NM_032523.4:c.718A>G

Variant names:

• chr2-178336361-A-G
• rs957888567
• NM_032523.4:c.718A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032523.4(OSBPL6):​c.718A>G​(p.Thr240Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T240S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSBPL6 NM_032523.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94
• Publications: 0 publications found

Genes affected

OSBPL6 (HGNC:16388): (oxysterol binding protein like 6) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074635655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032523.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL6	NM_032523.4	MANE Select	c.718A>G	p.Thr240Ala	missense	Exon 9 of 25	NP_115912.1	Q9BZF3-1
	OSBPL6	NM_001201480.2		c.718A>G	p.Thr240Ala	missense	Exon 9 of 26	NP_001188409.1	Q9BZF3-5
	OSBPL6	NM_145739.3		c.655A>G	p.Thr219Ala	missense	Exon 7 of 24	NP_665682.1	Q9BZF3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL6	ENST00000190611.9	TSL:1 MANE Select	c.718A>G	p.Thr240Ala	missense	Exon 9 of 25	ENSP00000190611.4	Q9BZF3-1
	OSBPL6	ENST00000392505.6	TSL:1	c.718A>G	p.Thr240Ala	missense	Exon 9 of 26	ENSP00000376293.2	Q9BZF3-5
	OSBPL6	ENST00000409631.5	TSL:1	c.718A>G	p.Thr240Ala	missense	Exon 8 of 23	ENSP00000386885.1	Q9BZF3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.045
Sift	Benign	0.33	T
Sift4G	Benign	0.72	T
Polyphen		0.31	B
Vest4		0.14
MutPred		0.14		Loss of glycosylation at T240 (P = 0.0127)
MVP		0.14
MPC		0.29
ClinPred		0.58	D
GERP RS		3.1
Varity_R		0.068
gMVP		0.30
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs957888567; hg19: chr2-179201088;